Effects of acetylsalicylic acid alone or with omega-3 in patients with chronic coronary artery disease

INTRODUCTION AND OBJECTIVES: Antiplatelet agents such as acetylsalicylic acid (ASA) play a prominent role in preventing atherothrombosis. However, low-responsive patients who will not benefit from an increased dosage of this drug, which can cause bleeding and gastrointestinal irritation, need to be identified. Drugs such as omega-3 fatty acids, which enhance the vasodilating condition and diminish platelet aggregation, can potentiate the anti-aggregating effects of ASA, avoiding its side effects. Thus, we assessed the alternative use of 200mg/day of ASA and 100mg/day of this drug combined with 1g of omega-3 in 152 patients with chronic coronary artery disease. METHODS: Our analysis included platelet function (ASPItest), TBX2 concentrations (ELISA), and SNPs polymorphisms in the rs3842787 and rs3842798 regions of the PTGS1 gene of the COX-1 enzyme and the rs5918 region of the ITGB3 gene of the fibrinogen's receptor subunit glycoprotein IIIa. RESULTS: ASPItest detected 38 non-responders. The reduction of ASPItest values was more significant in this group than in responders and fell to levels of responders in non-responders of the 200mg/day treatment. A rare allele of rs3842787 is associated with a worse ASPItest response, and the rare allele of the rs5918 polymorphism with a worse response related to TBX2 concentration. Both treatments showed no statistically significant difference in hematuria or bleeding, constituting safe treatment alternatives, and omega-3 treatment reduced monocyte levels. CONCLUSIONS: Our results underscore the usefulness of pharmacogenetics for personalized treatments, avoiding gastrointestinal effects and undesirable bleeding.

Efeito da nitroglicerina no espasmo e na oclusão da artéria radial em cateterismos transradiais realizados em mulheres / Effect of nitroglycerin on radial artery spasm and occlusion in transradial catheterizations performed in women

Introdução: O benefício do cateterismo transradial já foi confirmado em pacientes do sexo feminino. Mulheres submetidas a exames por cateterismo transradial apresentam desafios únicos. A ocorrência de espasmo e oclusão da artéria radial após o procedimento é maior em mulheres. Objetivamos avaliar o benefício da nitroglicerina na redução de espasmo e oclusão da artéria radial em mulheres submetidas a cateterismo transradial. Métodos: Estudo multicêntrico, prospectivo, randomizado 2x2 fatorial, duplo-cego. Participantes foram randomizados para nitroglicerina 500mcg ou placebo em dois momentos: após colocação do introdutor hemostático e antes da retirada. A avaliação de espasmo da artéria radial foi clínica, por meio de escala dor. A avaliação da oclusão da artéria radial foi realizada com Doppler, nas primeiras 12 horas. Resultados: Foram incluídos 2.040 pacientes, sendo 774 (37,5%) mulheres. A média de idade foi similar entre os sexos (62,2 anos versus 61,5 anos; p=0,27). A incidência de espasmo da artéria radial foi maior nas mulheres (21,2% versus 6,6%; p<0,01), bem como a incidência de oclusão da artéria radial (3,4% versus 1,8%; p=0,03). O uso da nitroglicerina no início do procedimento não reduziu a incidência de espasmo da artéria radial em mulheres quando comparado com o placebo (19,7% versus 22,6%; p=0,34), tampouco as taxas de oclusão da artéria radial (4,3% versus 2,5%; p=0,17). O uso da nitroglicerina ao fim do procedimento não reduziu a incidência de oclusão da artéria em mulheres (2,8% versus 3,9%; p=0,37). Conclusões: O espasmo e a oclusão da artéria radial são mais frequentes em mulheres submetidas a cateterismo transradial quando comparadas aos homens. O uso da nitroglicerina não apresenta efeito benéfico na redução dessas incidências.

Background: The benefit of transradial catheterization is well established in female patients. Women undergoing transradial catheterization exams present with unique challenges. The occurrence of radial artery spasm and occlusion after the procedure is higher in women. The objective of this study was to evaluate the benefit of nitroglycerin in reducing radial artery spasm and occlusion in women undergoing transradial catheterization. Methods: This was a 2x2 factorial randomized, multicenter, prospective, double-blinded study. Participants were randomized to nitroglycerin 500mcg or placebo at two time points: after placement of the hemostatic introducer and before its removal. The evaluation of the radial artery spasm was clinical, using a pain scale The evaluation of the radial artery occlusion was performed with Doppler, in the first 12 hours. Results: A total of 2,040 patients were included, of which 774 (37.5%) were female. Mean age was similar between sexes (62.2 years versus 61.5 years; p=0.27). The incidence of radial artery spasm was higher in women (21.2% versus 6.6%; p<0.01), as well as the incidence of radial artery occlusion (3.4% versus 1.8%; p=0.03). The use of nitroglycerin at the beginning of the procedure did not reduce the incidence of radial artery spasm in women when compared with placebo (19.7% versus 22.6%; p=0.34), nor did the rates of radial artery occlusion (4.3% versus 2.5%; p=0.17). The use of nitroglycerin at the end of the procedure did not reduce the incidence of artery occlusion in women (2.8% versus 3.9%; p=0.37). Conclusions: Radial artery spasm and occlusion are more frequent in women undergoing transradial catheterization when compared to men. The use of nitroglycerin does not have a beneficial effect in reducing these incidences.

Efeito da nitroglicerina no espasmo e oclusão da artéria radial em cateterismos transradiais realizados em mulheres / Effect of nitroglycerin on radial artery spasm and occlusion in transradial catheterizations performed in women

INTRODUÇÃO: O benefício do cateterismo por acesso transradial (ATR) já foi confirmado em pacientes do sexo feminino. As mulheres submetidas a exames por esta via de acesso apresentam desafios únicos, geralmente relacionados a um menor calibre arterial. A ocorrência de espasmo (EAR) e oclusão da artéria (OAR) após o procedimento também são descritas como maiores em mulheres. OBJETIVOS Avaliar o benefício do uso de nitroglicerina na redução de EAR e OAR em mulheres submetidas a ATR. MÉTODOS: Estudo multicêntrico, prospectivo, randomizado 2x2 fatorial, duplo-cego. Participantes foram randomizados para nitroglicerina 500 mcg ou placebo em dois momentos: após a colocação do introdutor hemostático e antes da retirada do introdutor. Todos os pacientes receberam hemostasia patente ou de pressão mínima. A avaliação de EAR foi clínica, através de escala numérica de dor (graduada de 0 a 10), e foi definida como presente nos casos em que seja maior que 6. A avaliação de OAR foi realizada com ultrassonografia com Doppler, realizada nas primeiras 12 horas após o procedimento. RESULTADOS: Foram incluídos 2040 pacientes, sendo 774 (37,5%) mulheres. A média de idade foi similar entre os sexos (62,2 anos vs. 61,5; p=0,27), mas as mulheres apresentaram maior IMC (29,3 vs. 28,1; p<0,01) e artérias radiais menores (2,33 mm vs. 2,74; p<0,01) A incidência de EAR foi maior nas mulheres (21,2% vs. 6,6%; p<0,01), bem como a incidência de OAR (3,4% vs. 1,8%; p=0,03). O uso da nitroglicerina no início do procedimento não reduziu a incidência de EAR em mulheres quando comparado com o placebo (19,7% vs. 22,6%; p=0,34), tão pouco as taxas de OAR (4,3% vs 2,5%; p=0,17). O uso da nitroglicerina ao final do procedimento não reduziu a incidência de OAR em mulheres (2,8% vs. 3,9%; p=0,37). CONCLUSÕES: O EAR e a OAR são mais frequentes em mulheres submetidas a cateterismo por ATR quando comparado aos homens. O uso da nitroglicerina não apresenta efeito benéfico na redução destas incidências, independente do momento de utilização.

Avaliação de espasmo e oclusão de artéria radial após cateterismo transradial, considerando o calibre de introdutor utilizado / Evaluation of radial artery spasm and occlusion after transradial catheterization, considering the sheath gauge used

INTRODUÇÃO: O benefício do cateterismo por acesso transradial (ATR) está bem estabelecido, principalmente em intervenções coronárias, onde o uso de medicações aumenta o risco de sangramento. O uso da via no cateterismo diagnóstico permite maior conforto ao paciente e reduz complicações relacionadas com a via de acesso. A ocorrência de espasmo (EAR) e oclusão da artéria (OAR) são as complicações mais frequentes do ATR. O uso de introdutores de menor calibre poderia reduzir estas complicações. OBJETIVOS: Comparar a incidência de EAR e OAR em cateterismo diagnósticos, considerando-se o calibre do introdutor utilizado. MÉTODOS: Estudo multicêntrico, prospectivo, observacional. A escolha do introdutor a ser utilizado ficou a cargo do médico responsável pelo procedimento. Todos pacientes receberam heparina na dose de 5000 UI e receberam hemostasia patente ou de pressão mínima ao final do procedimento. A avaliação de EAR foi clínica, através de escala numérica de dor (graduada de 0 a 10), e foi definido como presente nos casos em que seja maior que 6. A avaliação de OAR foi realizada com ultrassonografia com Doppler, realizada nas primeiras 12 horas após o procedimento. RESULTADOS: Foram incluídos 1534 pacientes submetidos a cateterismo diagnóstico, sendo 625 (40,7%) mulheres. A maioria dos procedimentos foi em síndromes coronárias crônicas (61,5%). Foram utilizados introdutores 5F em 1185 (77,2%) e 6 F em 349 (22.8%), todos os procedimentos foram concluídos com o introdutor inicialmente escolhido, sem necessidade de troca. A relação introdutor: artéria foi maior que 1 em 43,4% dos pacientes no grupo 5F e 39,3%, no grupo 6F (p=0,19). A incidência de EAR foi igual nos dois calibres de introdutores utilizados (11,4% vs. 12,3%; p=0,63), bem como a incidência de OAR (2,8% vs. 2,0%; p=0,42). CONCLUSÕES: O EAR e a OAR tem frequência similar em cateterismo diagnósticos realizados com introdutores 5F ou 6F. O papel do hemodinamicista na escolha do calibre a ser utilizado pode ter colaborado com este resultado, visto que não houve diferença na relação de calibre entre introdutor: artéria nos dois grupos, portanto um trabalho randomizado poderia não apresentar o mesmo resultado.

Genomics, epigenomics and pharmacogenomics of Familial Hypercholesterolemia (FHBGEP): A study protocol

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. SUMMARY: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients.

Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is one of the major causes of sudden cardiac death (SCD). An exon-targeted gene sequencing strategy was used to investigate the association of functional variants in sarcomeric genes (MYBPC3, MYH7 and TNNT2) with severe LVH and other SCD-related risk factors in Brazilian HCM patients. Clinical data of 55 HCM patients attending a Cardiology Hospital (Sao Paulo city, Brazil) were recorded. Severe LVH, aborted SCD, family history of SCD, syncope, non-sustained ventricular tachycardia and abnormal blood pressure in response to exercise were evaluated as SCD risk factors. Blood samples were obtained for genomic DNA extraction and the exons and untranslated regions of the MYH7, MYBPC3 and TNNT2 were sequenced using Nextera® and MiSEq® reagents. Variants were identified and annotated using in silico tools, and further classified as pathogenic or benign according to the American College of Medical Genetics and Genomics guidelines. Variants with functional effects were identified in MYBPC3 (n = 9), MYH7 (n = 6) and TNNT2 (n = 4). The benign variants MYBPC3 p.Val158Met and TNNT2 p.Lys263Arg were associated with severe LVH (p < 0.05), and the MYH7 p.Val320Met (pathogenic) was associated with family history of SCD (p = 0.037). Increased risk for severe LVH was found in carriers of MYBPC3 Met158 (c.472 A allele, OR = 13.5, 95% CI = 1.80-101.12, p = 0.011) or combined variants (MYBPC3, MYH7 and TNNT2: OR = 12.39, 95% CI = 2.14-60.39, p = 0.004). Carriers of TNNT2 p.Lys263Arg and combined variants had higher values of septum thickness than non-carriers (p < 0.05). Molecular modeling analysis showed that MYBPC3 158Met reduces the interaction of cardiac myosin-binding protein C (cMyBP-C) RASK domain (amino acids Arg215-Ala216-Ser217-Lys218) with tropomyosin. In conclusion, the variants MYBPC3 p.Val158Met, TNNT2 p.Lys263Arg and MYH7 p.Val320Met individually or combined contribute to the risk of sudden cardiac death and other outcomes of hypertrophic cardiomyopathy.

Association of variants in MYH7, MYBPC3 and TNNT2 with sudden cardiac death-related risk factors in Brazilian patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by unexplained left ventricular hypertrophy (LVH) and is one of the major causes of sudden cardiac death (SCD). An exon-targeted gene sequencing strategy was used to investigate the association of functional variants in sarcomeric genes (MYBPC3, MYH7 and TNNT2) with severe LVH and other SCD-related risk factors in Brazilian HCM patients. Clinical data of 55 HCM patients attending a Cardiology Hospital (Sao Paulo city, Brazil) were recorded. Severe LVH, aborted SCD, family history of SCD, syncope, non-sustained ventricular tachycardia and abnormal blood pressure in response to exercise were evaluated as SCD risk factors. Blood samples were obtained for genomic DNA extraction and the exons and untranslated regions of the MYH7, MYBPC3 and TNNT2 were sequenced using Nextera® and MiSEq® reagents. Variants were identified and annotated using in silico tools, and further classified as pathogenic or benign according to the American College of Medical Genetics and Genomics guidelines. Variants with functional effects were identified in MYBPC3 (n = 9), MYH7 (n = 6) and TNNT2 (n = 4). The benign variants MYBPC3 p.Val158Met and TNNT2 p.Lys263Arg were associated with severe LVH (p < 0.05), and the MYH7 p.Val320Met (pathogenic) was associated with family history of SCD (p = 0.037). Increased risk for severe LVH was found in carriers of MYBPC3 Met158 (c.472 A allele, OR = 13.5, 95% CI = 1.80-101.12, p = 0.011) or combined variants (MYBPC3, MYH7 and TNNT2: OR = 12.39, 95% CI = 2.14-60.39, p = 0.004). Carriers of TNNT2 p.Lys263Arg and combined variants had higher values of septum thickness than non-carriers (p < 0.05). Molecular modeling analysis showed that MYBPC3 158Met reduces the interaction of cardiac myosin-binding protein C (cMyBP-C) RASK domain (amino acids Arg215-Ala216-Ser217-Lys218) with tropomyosin. In conclusion, the variants MYBPC3 p.Val158Met, TNNT2 p.Lys263Arg and MYH7 p.Val320Met individually or combined contribute to the risk of sudden cardiac death and other outcomes of hypertrophic cardiomyopathy.

Genomics, epigenomics and pharmacogenomics of familial hypercholesterolemia (FHBGEP): A study protocol.

BACKGROUND: Familial hypercholesterolemia (FH) is a genetic disease that affects millions of people worldwide. OBJECTIVES: The study protocol FHBGEP was design to investigate the main genomic, epigenomic, and pharmacogenomic factors associated with FH and polygenic hypercholesterolemia (PH). METHODS: FH patients will be enrolled at six research centers in Brazil. An exon-targeted gene strategy will be used to sequence a panel of 84 genes related to FH, PH, pharmacogenomics and coronary artery disease. Variants in coding and regulatory regions will be identified using a proposed variant discovery pipeline and classified according to the American College Medical Genetics guidelines. Functional effects of variants in FH-related genes will be investigated by in vitro studies using lymphocytes and cell lines (HepG2, HUVEC and HEK293FT), CRISPR/Cas9 mutagenesis, luciferase reporter assay and other technologies. Functional studies in silico, such as molecular docking, molecular dynamics, and conformational analysis, will be used to explore the impact of novel variants on protein structure and function. DNA methylation profile and differential expression of circulating non-coding RNAs (miRNAs and lncRNAs) will be analyzed in FH patients and normolipidemic subjects (control group). The influence of genomic and epigenomic factors on metabolic and inflammatory status will be analyzed in FH patients. Pharmacogenomic studies will be conducted to investigate the influence of genomic and epigenomic factors on response to statins in FH patients. SUMMARY: The FHBGEP protocol has the potential to elucidate the genetic basis and molecular mechanisms involved in the pathophysiology of FH and PH, particularly in the Brazilian population. This pioneering approach includes genomic, epigenomic and functional studies, which results will contribute to the improvement of the diagnosis, prognosis and personalized therapy of FH patients.

Predictive role of Selvester QRS score in patients undergoing transcatheter aortic valve replacement

INTRODUCTION: Few data exist regarding the late clinical impact of the Selvester score prediction of myocardial fibrosis after transcatheter aortic valve replacement (TAVR). This study evaluated the predictive power of the Selvester score on survival in patients with aortic stenosis (AS) undergoing TAVR. METHODS And Results: Patients with severe AS who had preoperative electrocardiograms were included. Clinical follow-up was obtained retrospectively. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular death and major adverse cardiac events (MACEs). Two-hundred twenty-eight patients were included (mean age, 81.5 ± 7.4 years; women, 58.3%). Deceased patients had a higher mean score (4.6 ± 3.2 vs. 1.4 ± 1.3; p < .001). At a mean follow-up of 36.2 ± 21.2 months, the Selvester score was independently associated with all-cause mortality (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.48-1.84; p < .001), cardiovascular death (HR, 1.59; 95% CI, 1.38-1.74; p < .001), and MACE (HR, 1.55; 95% CI, 1.30-1.68; p < .001). After 5 years, the mortality risk was incrementally related to the Selvester score. The involvement of the inferior wall of the left ventricle was a lower mortality risk factor (HR, 0.42; 95% CI, 0.18-0.98; p = .046). For a Selvester score of 3, the area under the curve showed 0.92, 0.94, and 0.86 (p < .001), respectively, for 1, 2, and 3 years. CONCLUSIONS: Elevated Selvester scores increase the risk of poor outcomes in patients with AS undergoing TAVR. The involvement of the anterior or lateral wall presents worse prognosis.

Ultrasound study of forearm arteries in patients undergoing cardiac catheterization, and assessment of predictors of arterial vessel caliber

BACKGROUND: The radial approach has been increasingly used worldwide for diagnostic and therapeutic cardiac catheterization. The radial artery caliber is one of the limitations of its use. The objective of this study was to describe the anatomy of the radial and ulnar arteries, as well as to develop a radial artery diameter prediction score using clinical and anthropometric criteria. METHODS: Using vascular ultrasound with bilateral radial and ulnar artery measurements, 1,180 patients who underwent cardiac catheterization or angioplasty procedures were prospectively evaluated. Using the patients' variables, a radial artery diameter prediction score was developed in a cross-sectional fashion, using half of the sample. The score was validated with the half not used for deriving the model. RESULTS: A total of 1,180 patients were evaluated. The mean internal diameter of the right and left radial arteries was 2.69±0.69mm and 2.53±0.64mm (p<0.01), and the mean internal diameter of the right and left ulnar arteries was 2.09±0.59mm and 2.10±0.60mm (p=0.76), respectively. The factors that positively correlated with arterial size were male sex, previous catheterization, height, weight, and body surface area. The risk score developed using clinical and anthropometric variables had unsatisfactory discriminatory capacity (c-statistics 0.64). CONCLUSION: The right radial artery is the largest forearm artery in most cases. Men and patients who had previously undergone catheterization have a larger mean radial artery diameter. The artery diameter prediction score has modest accuracy for clinical use. (AU)

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients.

BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1ß, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1ß plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1ß secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1ß plasma concentrations could be used to the early identification of RD patients.

Increased levels of plasma IL-1b and BDNF can predict resistant depression patients

SUMMARY BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

RESUMO FUNDAMENTAÇÃO: Não há fortes evidências sobre a associação entre o perfil inflamatório e o padrão de resposta ao tratamento medicamentoso em pacientes depressivos que podem resultar em ocorrência de doença coronariana. OBJETIVO: O objetivo deste estudo foi comparar os marcadores de aterosclerose subclínica, o perfil inflamatório e a produção de BDNF em pacientes com Depressão Resistente (DR) ou Transtorno Afetivo Bipolar (BAD) sob tratamento convencional. MÉTODOS: A população avaliada incluiu 34 RD, 43 BAD e 41 controles. Os marcadores de aterosclerose subclínica foram avaliados por ultrassonografia, tomografia e teste de esforço. As concentrações plasmáticas de TNFα, IL-1β, IL-6 e BDNF foram medidas utilizando Luminex100TM. A concentração de usCRP foi medida por imunoensaio turbidimétrico. A expressão de IL1B, IL6 e TNFA foi determinada usando TaqMan®. Para as análises estatísticas, foi estabelecido o nível de significância de p < 0,05. RESULTADOS: Quanto aos marcadores de aterosclerose subclínica, apenas o consumo de O2 foi reduzido no grupo BAD (p = 0,001). Embora não tenham sido encontradas diferenças na expressão gênica, a concentração plasmática de BDNF e IL-1β foi aumentada no grupo RD (p = 0,002 e p = 0,005, respectivamente) mesmo sob tratamento antidepressivo, o que sugere que esses medicamentos não têm efeito na secreção de IL-1β e que o inflamassomo pode desempenhar um papel na resposta terapêutica. CONCLUSÃO: Juntas, as concentrações BDNF e IL-1β poderiam ser usadas para a identificação precoce de pacientes com DR.

Correlation between venous pressure gradients and intravascular ultrasound in the diagnosis of iliac vein compression syndrome

Objective: The objective of this study was to evaluate the correlation between venous pressure gradients (VPGs) and intravascular ultrasound (IVUS) for the diagnosis of caval-iliac venous obstructions in patients with advanced chronic venous insufficiency. Methods: Fifty patients with advanced chronic venous insufficiency symptoms (Clinical, Etiology, Anatomy, and Pathophysiology class 3 to 6) were prospectively submitted to multiplanar venography (MV) with intravenous pressure measurements and IVUS. The patients' lower limbs were divided accordingly: group I, limbs with <50% obstruction on IVUS (n » 49); and group II, limbs with $50% obstruction on IVUS (n » 51). Receiver operating characteristic curves compared the diagnostic performance of the VPGs. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy assessed the performance of VPGs in categories to determine the presence of significant obstruction. Logistic regression assessed the capacity of the VPGs to identify significant obstruction. Results: The most frequent point of venous compression according to IVUS was the proximal left common iliac vein (70%; P < .05). Group II showed a greater prevalence of transpelvic (group I, 8.2%; group II, 74.5%; P < .001) and paravertebral collaterals (group I, 4.1%; group II, 45.1%; P < .001) on n MV. The femoral vein pressures at rest and after reactive hyperemia as well as the femorocaval gradient after reactive hyperemia (FCG-rh) and the femoral gradient after reactive hyperemia were significantly higher in group II (P » .001, P < .001, P » .002, and P » .006). The FCG-rh and the femoral gradient after reactive hyperemia presented the best diagnostic performance among the VPGs (P » .004 and P » .007) in n the receiver operating characteristic curve analysis, although no significant differences between them were found. All the gradients presented low values of sensitivity (<40%). negative predictive value (<60%). and accuracy (<30%). Logistic regression showed that FCG-rh was significantly independent of MV (OR, 8.1; P » .011) in identifying significant obstructions. Conclusions: There is correlation between the VPGs and significant obstructions with IVUS. However, this correlation does not translate to a good diagnostic performance of these VPGs. Only the FCG-rh added significant information to MV in identifying significant caval-iliac vein obstructions.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome The SECURE-PCI Randomized Clinical Trial

IMPORTANCE The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. OBJECTIVE To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. DESIGN, SETTING, AND PARTICIPANTS Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. INTERVENTIONS Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. MAIN OUTCOMES AND MEASURES The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. RESULTS Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, −0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. CONCLUSIONS AND RELEVANCE Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

Importance: The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. Objective: To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Interventions: Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Results: Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Conclusions and Relevance: Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. Trial Registration: clinicaltrials.gov Identifier: NCT01448642.

Prospective, double-blind, randomized controlled trial comparing electrocoagulation and radiofrequency in the treatment of patients with great saphenous vein insufficiency and lower limb varicose veins

OBJECTIVE: Thermoablation has been replacing conventional surgery in the surgical treatment of great saphenous vein (GSV) reflux in patients with lower limb varicose veins; however, thermoablation is expensive. Intravenous electrocoagulation (EC) may, selectively and safely, cause necrosis of the GSV wall, but the clinical results have never been studied. The objective of this study was to compare EC and radiofrequency ablation (RFA) in the treatment of GSV insufficiency, considering efficacy, complications, and effect on quality of life.METHODS:This was a prospective, double-blind, randomized clinical trial. Patients with lower limb varicose veins and GSV reflux confirmed by duplex ultrasound were randomized into two treatment groups: EC and RFA. Patients were followed up at 1 week, 3 months, and 6 months after the procedure. Occlusion of the GSV confirmed by duplex ultrasound was considered the primary outcome, and the rate of complications and improvement in quality of life, using the Aberdeen Varicose Vein Questionnaire score, were the secondary outcomes...

Perfil contemporâneo da intervenção coronária percutânea em octogenários / Contemporary profile of percutaneous coronary intervention in octogenarians

INTRODUÇÃO: Com o aumento da longevidade observado nas últimas décadas, as intervenções coronárias percutâneas (ICP) em octogenários são cada vez mais indicadas. OBJETIVO: Traçar o perfil clínico-epidemiológico-angiográfico e os principais detalhes associados à ICP dos pacientes octogenários. MÉTODOS: Cento e cinquenta pacientes octogenários foram submetidos à ICP entre janeiro de 2015 a dezembro de 2016, no Instituto Dante Pazzanese de Cardiologia, correspondendo a 3,7% dos 3987 casos tratados e a 18% dos com idade >70 anos, e incluídos de forma sequencial e prospectiva. Não houve critérios de exclusão. Os resultados clínicos expostos foram restritos à fase hospitalar. RESULTADOS: A maioria (63%) era do sexo masculino, com idade média de 86±3,9 anos (máximo de 102 anos). Do total de pacientes, 91,3% eram hipertensos, 37,4% diabéticos, a ICP prévia foi realizada em para 17,4%, enquanto 34,1% apresentaram infarto prévio. A cinecoronariografia identificou que 70,4% eram multiarteriais, dos quais 4% exibiam lesões não protegidas do tronco da coronária esquerda. A maioria (55%) apresentava disfunção ventricular significativa. Stents farmacológicos (SF) foram utilizados em 97,2% dos casos. O sucesso angiográfico foi obtido em 97,5% e o sucesso clínico em 93,2%. A mortalidade e o infarto ocorreram abaixo de 4,3% dos casos. CONCLUSÃO: Nessa população, observaram-se que os pacientes octogenários constituíram a minoria dos idosos tratados; a doença multiarterial grave foi o achado predominante; os stents farmacológicos foram implantados quase em todos os casos e os sucessos angiográfico e clínico apresentaram-se elevados. (AU)

INTRODUCTION: With the increase in longevity observed in recent decades, percutaneous coronary interventions (PCI) in octogenarians are increasingly indicated. OBJECTIVE: To outline the clinical, epidemiological and angiographic profile and main details associated with PCI in octogenarian patients. METHODS: One hundred and fifty octogenarian patients underwent PCI between January 2015 and December 2016 at the Dante Pazzanese Institute of Cardiology, corresponding to 3.7% of the 3987 cases treated and 18% of those aged> 70 years, and included sequentially and prospectively. There were no exclusion criteria. The clinical results were restricted to the hospital phase. RESULTS: The majority (63%) were males, with a mean age of 86±3.9 years (maximum 102 years). Of the total patients, 91.3% were hypertensive, 37.4% were diabetic, 17.4% had previously undergone PCI, while 34.1% had previous infarction. The coronary angiography indicated that 70.4% were multiarterial, of which 4% had unprotected lesions of the trunk of the left coronary artery. The majority (55%) had significant ventricular dysfunction. Pharmacological stents were used in 97.2% of the cases. Angiographic success was achieved in 97.5% and clinical success in 93.2%. Mortality and infarction occurred in less than 4.3% of the cases. CONCLUSION: In this population, it was observed that octogenarian patients constituted a minority of treated elderly; severe multivessel disease was the predominant finding; pharmacological stents were implanted in almost all cases, and angiographic and clinical success rates were high. (AU)

Perfil contemporâneo da intervenção coronária percutânea em octogenários / Contemporary profile of percutaneous coronary intervention in octogenarians

Introdução: Com o aumento da longevidade observado nas últimas décadas, as intervenções coronárias percutâneas (ICP) em octogenários são cada vez mais indicadas. Objetivo: Traçar o perfil clínico-epidemiológico-angiográfico e os principais detalhes associados à ICP dos pacientes octogenários. Métodos: Cento e cinquenta pacientes octogenários foram submetidos à ICP entre janeiro de 2015 a dezembro de 2016, no Instituto Dante Pazzanese de Cardiologia, correspondendo a 3,7% dos 3987 casos tratados e a 18% dos com idade >70 anos, e incluídos de forma sequencial e prospectiva. Não houve critérios de exclusão. Os resultados clínicos expostos foram restritos à fase hospitalar. Resultados: A maioria (63%) era do sexo masculino, com idade média de 86±3,9 anos (máximo de 102 anos). Do total de pacientes, 91,3% eram hipertensos, 37,4% diabéticos, a ICP prévia foi realizada em para 17,4%, enquanto 34,1% apresentaram infarto prévio. A cinecoronariografia identificou que 70,4% eram multiarteriais, dos quais 4% exibiam lesões não pro - tegidas do tronco da coronária esquerda. A maioria (55%) apresentava disfunção ventricular significativa. Stents farmacológicos (SF) foram utilizados em 97,2% dos casos. O sucesso angiográfico foi obtido em 97,5% e o sucesso clínico em 93,2%. A mortalidade e o infarto ocorreram abaixo de 4,3% dos casos. Conclusão: Nessa população, observaram-se que os pacientes octogenários constituíram a minoria dos idosos tratados; a doença multiarterial grave foi o achado predominante; os stents farmacológicos foram implantados quase em todos os casos e os sucessos angiográfico e clínico apresentaram-se elevado

With the increase in longevity observed in recent decades, percutaneous coronary interventions (PCI) in octogenarians are increasingly indicated. Objective: To outline the clinical, epidemiological and angiographic profile and main details associated with PCI in octogenarian patients. Methods: One hundred and fifty octogenarian patients underwent PCI between January 2015 and December 2016 at the Dante Pazzanese In - stitute of Cardiology, corresponding to 3.7% of the 3987 cases treated and 18% of those aged> 70 years, and included sequentially and prospectively. There were no exclusion criteria. The clinical results were restricted to the hospital phase. Results: The majority (63%) were males, with a mean age of 86±3.9 years (maximum 102 years). Of the total patients, 91.3% were hypertensive, 37.4% were diabetic, 17.4% had previously undergone PCI, while 34.1% had previous infarction. The coronary angiography indicated that 70.4% were multiarterial, of which 4% had unprotected lesions of the trunk of the left coronary artery. The majority (55%) had significant ventricular dysfunction. Pharmacological stents were used in 97.2% of the cases. Angiographic success was achieved in 97.5% and clinical success in 93.2%. Mortality and infarction occurred in less than 4.3% of the cases. Conclusion: In this population, it was observed that octogenarian patients constituted a minority of treated elderly; severe multivessel disease was the predominant finding; pharmacological stents were implanted in almost all cases, and angiographic and clin